nat does lidocaine do to voltage-gated Na* channels? How does the effect of lidocaine differ from the effect

Lidocaine is a local anesthetic that primarily works by blocking voltage-gated sodium (Na⁺) channels in neurons, which is crucial for the initiation and propagation of action potentials. When lidocaine binds to these sodium channels, it stabilizes the inactivated state of the channel, effectively preventing the influx of sodium ions during depolarization. This blockade results in reduced excitability and conduction of nerve impulses, leading to local anesthesia.

In terms of its action on voltage-gated sodium channels, lidocaine typically exhibits the following characteristics:

1. Use-dependent block: The blockade of sodium channels by lidocaine is more pronounced when channels are in the activated or inactivated state. This means that during rapid firing of action potentials, more lidocaine can bind to and block the channels, making it especially effective in conditions of increased neuronal activity.

2. Reversible binding: The effect of lidocaine is reversible, and the sodium channels can recover from blockade once the drug is cleared or when the membrane potential returns to resting levels.

In contrast, a drug like TTX (tetrodotoxin) has a different mechanism of action on voltage-gated sodium channels:

1. Non-use-dependent block: TTX binds to a specific site on the outside of the sodium channel, blocking it regardless of whether the channel is in a resting, activated, or inactivated state. This means that TTX can block sodium channels without depending on the membrane potential or the frequency of action potentials.

2. Irreversible block: The interaction of TTX with sodium channels is so potent that it can effectively render the channels inoperable as long as TTX is present. This results in a complete prevention of action potentials, leading to paralysis and potentially fatal consequences if used systemically.

In summary, the primary differences are:

• Lidocaine: use-dependent and reversible blockade of Na⁺ channels, primarily affecting excited neurons.
• TTX: non-use-dependent and highly potent blockade, effectively shutting down action potentials in affected neurons regardless of their state.